The current use of topical fluoride (F) agents is largely empirically based, and there is a need to establish the optimal range of F concentrations in oral fluids necessary to prevent dental caries. The long-term objective of this study is to determine the relationship between F levels present in oral fluids and enamel demineralization and remineralization. The research will involve the use of an intraoral caries model to study two phenomena which have been strongly associated with the clinical effectiveness of fluoride, namely, prevention of enamel demineralization and enhancement of enamel remineralization as measured by changes in surface microhardness. Fluoride (F) levels in whole saliva, site-specific saliva samples and site-specific whole plaque and plaque fluid samples will be monitored over experimental periods each lasting 1, 7 and 14 days. Fluoride uptake by partially demineralized enamel blocks will also be determined. A panel of 20 subjects who are partial denture wearers will participate in all aspects of the study. Two gauze-covered enamel blocks, one sound (to study demineralization) and one partially demineralized (to study remineralization), will be placed on each side of the appliance in the buccal sulcus area. In the first phase of the project, an intraoral demin/remin model will be used to study the effect of intermittent fluoride exposure by comparing four dentifrices containing 0, 250, 500 and 1 100 ppm F. In the second phase, the effect of continuous low levels of F exposure will be studied by using intraoral fluoride-releasing devices (IFRDs) targeted to release approximately 0, 0.05, 0.10 and 0.20 mg F/day into the mouth, and thus achieve levels of F in saliva of 0.03, 0.1, 0.2 and 0.4 ppm (mg/L) F, respectively. The devices will be mounted in the buccal flange area on each side of the subject's partial denture between the two test enamel blocks, to achieve the most consistent level of F exposure. The specific aims are to: 1. validate the intraoral demin/remin model by comparing the results from the present dose/response study using dentifrices with data from previously published clinical caries trials; 2. establish the optimal range of F concentrations in oral fluids (saliva, plaque fluid) necessary to prevent demineralization of sound enamel and enhance remineralization of partially demineralized enamel; 3. to compare the anticaries effects of intermittent F exposure from F dentifrice with continuous F exposure from IFRDs; 4. to establish the oral distribution pattern of F in the mouth from IFRDs. The findings from the proposed studies should provide a scientific basis for the development of improved systems which deliver optimal levels of topical F to sites at risk with minimal systemic F exposure.